Distinct role of PLCβ3 in VEGF-mediated directional migration and vascular sprouting

被引：50

作者：

Bhattacharya, Resham ^{[1
]}

Kwon, Junhye ^{[1
]}

Li, Xiujuan ^{[2
]}

Wang, Enfeng ^{[1
]}

Patra, Sujata ^{[1
]}

Bida, John Paul ^{[1
]}

Bajzer, Zeljko ^{[1
]}

Claesson-Welsh, Lena ^{[2
]}

Mukhopadhyay, Debabrata ^{[1
]}

机构：

[1] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA

[2] Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, S-75185 Uppsala, Sweden

来源：

JOURNAL OF CELL SCIENCE | 2009年 / 122卷 / 07期

关键词：

Migration; Proliferation; Endothelial signaling; PLC beta 3; ENDOTHELIAL-GROWTH-FACTOR; PHOSPHOLIPASE-C ISOZYMES; PERMEABILITY-FACTOR; CELL-MIGRATION; G-PROTEINS; FACTOR RECEPTOR-2; TUMOR-CELLS; ANGIOGENESIS; PHOSPHORYLATION; ACTIVATION;

D O I：

10.1242/jcs.041913

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Endothelial cell proliferation and migration is essential to angiogenesis. Typically, proliferation and chemotaxis of endothelial cells is driven by growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). VEGF activates phospholipases (PLCs) specifically PLC gamma 1 - that are important for tubulogenesis, differentiation and DNA synthesis. However, we show here that VEGF, specifically through VEGFR2, induces phosphorylation of two serine residues on PLC beta 3, and this was confirmed in an ex vivo embryoid body model. Knockdown of PLC beta 3 in HUVEC cells affects IP3 production, actin reorganization, migration and proliferation; whereas migration is inhibited, proliferation is enhanced. Our data suggest that enhanced proliferation is precipitated by an accelerated cell cycle, and decreased migration by an inability to activate CDC42. Given that PLC beta 3 is typically known as an effector of heterotrimeric G-proteins, our data demonstrate a unique crosstalk between the G-protein and receptor tyrosine kinase (RTK) axes and reveal a novel molecular mechanism of VEGF signaling and, thus, angiogenesis.

引用

页码：1025 / 1034

页数：10

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